1-43975861-A-G

Position:

• chr1-43975861-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004047.5(ATP6V0B):​c.116+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,587,268 control chromosomes in the GnomAD database, including 3,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.070 (430 hom., cov: 33)
  • Exomes 𝑓: 0.058 (2885 hom.)
• Consequence: ATP6V0B NM_004047.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291

Genes affected

ATP6V0B (HGNC:861): (ATPase H+ transporting V0 subunit b) This gene encodes a portion of the V0 domain of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Activity of this enzyme is necessary for such varied processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V0B	NM_004047.5	c.116+13A>G		intron_variant		ENST00000472174.7	NP_004038.1
ATP6V0B	XM_047422650.1	c.-139A>G		5_prime_UTR_variant	1/7		XP_047278606.1
ATP6V0B	NM_001039457.3	c.-25-229A>G		intron_variant			NP_001034546.1
ATP6V0B	NM_001294333.2	c.116+13A>G		intron_variant			NP_001281262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V0B	ENST00000472174.7	c.116+13A>G		intron_variant		1	NM_004047.5	ENSP00000431605	P1

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10624 AN: 152084 Hom.: 429 Cov.: 33

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0714

Gnomad ASJ AF: 0.0485

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0779

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0775

GnomAD3 exomes AF: 0.0679 AC: 15722 AN: 231558 Hom.: 731 AF XY: 0.0675 AC XY: 8440 AN XY: 124976

Gnomad AFR exome AF: 0.0929

Gnomad AMR exome AF: 0.0747

Gnomad ASJ exome AF: 0.0408

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.0782

Gnomad FIN exome AF: 0.0301

Gnomad NFE exome AF: 0.0521

Gnomad OTH exome AF: 0.0637

GnomAD4 exome AF: 0.0582 AC: 83489 AN: 1435066 Hom.: 2885 Cov.: 32 AF XY: 0.0583 AC XY: 41452 AN XY: 711448

Gnomad4 AFR exome AF: 0.0956

Gnomad4 AMR exome AF: 0.0730

Gnomad4 ASJ exome AF: 0.0448

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.0752

Gnomad4 FIN exome AF: 0.0297

Gnomad4 NFE exome AF: 0.0528

Gnomad4 OTH exome AF: 0.0653

GnomAD4 genome AF: 0.0699 AC: 10642 AN: 152202 Hom.: 430 Cov.: 33 AF XY: 0.0705 AC XY: 5249 AN XY: 74408

Gnomad4 AFR AF: 0.0964

Gnomad4 AMR AF: 0.0717

Gnomad4 ASJ AF: 0.0485

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0782

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0533

Gnomad4 OTH AF: 0.0805

Alfa AF: 0.0574 Hom.: 290

Bravo AF: 0.0732

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.1
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2286243; hg19: chr1-44441533; COSMIC: COSV52542880; COSMIC: COSV52542880;